Excellence in Research: Developmental regulation of WDR77 coordinates prostate growth and differentiation during the development through puberty

卓越研究：WDR77 的发育调节可协调青春期发育期间的前列腺生长和分化

• 批准号: 2300390
• 负责人: Zhengxin Wang
• 金额: $ 91.4万
• 依托单位: Clark Atlanta University
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-08-01 至 2027-07-31
• 项目状态: 未结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2300390&HistoricalAwards=false
• 关键词: Excellence; Research; Developmental; regulation; WDR77

This research will address how altered male hormone levels during development through puberty affect growth and differentiation of the prostate gland. The project will first determine whether male hormone at lower levels (during puberty) leads to growth of the prostate gland and, in contrast, if higher levels of the male hormone (post-puberty) promote the prostate’s differentiation. The research will then investigate how the male hormone’s action is switched during prostate development throughout puberty. The proposed research represents a novel study concept that relates to the basic biology of prostate development. The various age-related diseases in older adult prostate reflect the loss of developmental coordination of cell proliferation and differentiation. Therefore, the research may also help to understand the development of various prostatic diseases in older men. The project will also directly support graduate and undergraduate student training and promote scientific research in a minority population at this HBCU.The mammalian prostate gland passes through several phases of rapid growth and differentiation during development. The molecular mechanisms that determine growth and differentiation stages, as well as coordinating these two processes are less defined. This research will address these critical questions. The goal of the project is to study molecular events and mechanisms that coordinate cell growth and differentiation during prostate development from adolescent (proliferating) to young adult (quiescent/differentiated) stage. The research will first investigate the androgen function in a dosage-dependent manner to control growth and differentiation of the prostate during mouse development through puberty. A concentration threshold at which the androgen action is switched from growth promotion to growth inhibition/differentiation will be determined. Previous studies have identified the WDR77 protein localized in the cytoplasm at the early (during puberty, proliferating) stage of the prostate development drives cell proliferation. In adult (post-puberty, quiescent/differentiated) prostate, the protein in the nucleus functions as an androgen receptor cofactor to promote cell differentiation. The research will then investigate whether WDR77 mediates the androgen’s role to coordinate growth and differentiation during the prostate development. How change of androgen levels alters epigenetic modifications, leading to altered expression of AR-target genes as well as WDR77 subcellular localization will be studied using chromatin immunoprecipitation and gene promoter mapping.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

通过青春期开发过程中的男性如何改变了男性，他的项目首先会确定雄性激素在水平（青春期）是否会导致前列腺的增长和相反的雄性激素。 CTION的开发是对拟议的研究。老年男性的各种生产疾病都支持毕业生和地下学生培训，并促进哺乳动物前列腺的少数族裔研究经历了快速增长和开发过程中的分子机制。该项目的定义较少。小鼠发育期间的阈值，静止的前列腺，核的作用为雄激素受体辅助因子，以促进WDR77的细胞差异。染色质免疫沉淀和启动子映射。该奖项反映了NSF的法定任务，并通过基金会的知识分子优点和更广泛的不良影响对审查标准进行评估而获得了值得支持的支持。